Efficacy and Safety of The Albumin-Bound Paclitaxel Combined with Anti-PD-1 Antibody in Pancreatic Ductal Adenocarcinoma

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy with limited response to chemotherapy and immune checkpoint inhibitors (ICIs). This study evaluates the efficacy and safety of combining Albumin-Bound Paclitaxel (nab-PTX) with an anti-PD-1 antibody and aims to identify potential biomarkers to optimize therapeutic outcomes. The murine model of PDAC is established by subcutaneously injecting the murine pancreatic cancer cell line Panc02 into C57BL/6J mice. The mice are treated with either an anti-PD-1 antibody, nab-PTX, or nab-PTX plus anti-PD-1 antibody, with untreated mice serving as the control. Tumor growth, immune cell infiltration, cytokine levels, overall survival, organ damage, and gene expression profiles are analyzed. The combination therapy shows superior efficacy compared to nab-PTX and non-inferior efficacy compared to the anti-PD-1 antibody. Moreover, this strategy significantly reduces the risk of irAEs and hyperprogression caused by the anti-PD-1 antibody. In addition, screening identifies WNT9a as a potential gene associated with improved efficacy and ATF3 with enhanced safety, providing valuable insights for optimizing therapeutic strategies in PDAC.